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Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells

The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer‐associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts a...

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Autores principales: Kryza, Thomas, Silva, Lakmali M., Bock, Nathalie, Fuhrman‐Luck, Ruth A., Stephens, Carson R., Gao, Jin, Samaratunga, Hema, Lawrence, Mitchell G., Hooper, John D., Dong, Ying, Risbridger, Gail P., Clements, Judith A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623815/
https://www.ncbi.nlm.nih.gov/pubmed/28510269
http://dx.doi.org/10.1002/1878-0261.12075
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author Kryza, Thomas
Silva, Lakmali M.
Bock, Nathalie
Fuhrman‐Luck, Ruth A.
Stephens, Carson R.
Gao, Jin
Samaratunga, Hema
Lawrence, Mitchell G.
Hooper, John D.
Dong, Ying
Risbridger, Gail P.
Clements, Judith A.
author_facet Kryza, Thomas
Silva, Lakmali M.
Bock, Nathalie
Fuhrman‐Luck, Ruth A.
Stephens, Carson R.
Gao, Jin
Samaratunga, Hema
Lawrence, Mitchell G.
Hooper, John D.
Dong, Ying
Risbridger, Gail P.
Clements, Judith A.
author_sort Kryza, Thomas
collection PubMed
description The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer‐associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein‐related peptidase‐4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF‐like features in the prostate‐derived WPMY1 normal stromal cell line, including increased expression of alpha‐smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease‐activated receptor‐1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient‐derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial‐derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment.
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spelling pubmed-56238152017-10-04 Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells Kryza, Thomas Silva, Lakmali M. Bock, Nathalie Fuhrman‐Luck, Ruth A. Stephens, Carson R. Gao, Jin Samaratunga, Hema Lawrence, Mitchell G. Hooper, John D. Dong, Ying Risbridger, Gail P. Clements, Judith A. Mol Oncol Research Articles The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer‐associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein‐related peptidase‐4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF‐like features in the prostate‐derived WPMY1 normal stromal cell line, including increased expression of alpha‐smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease‐activated receptor‐1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient‐derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial‐derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. John Wiley and Sons Inc. 2017-08-10 2017-10 /pmc/articles/PMC5623815/ /pubmed/28510269 http://dx.doi.org/10.1002/1878-0261.12075 Text en © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kryza, Thomas
Silva, Lakmali M.
Bock, Nathalie
Fuhrman‐Luck, Ruth A.
Stephens, Carson R.
Gao, Jin
Samaratunga, Hema
Lawrence, Mitchell G.
Hooper, John D.
Dong, Ying
Risbridger, Gail P.
Clements, Judith A.
Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
title Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
title_full Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
title_fullStr Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
title_full_unstemmed Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
title_short Kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
title_sort kallikrein‐related peptidase 4 induces cancer‐associated fibroblast features in prostate‐derived stromal cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623815/
https://www.ncbi.nlm.nih.gov/pubmed/28510269
http://dx.doi.org/10.1002/1878-0261.12075
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